Production of thienylsodium compounds



Dec. 27, 1949 J. w. SCHICK 0 PRODUCTION OF THIEN YLSODIUM COMPOUNDS Filed Nov. 14, 1946 ML OF SOLVENT PER MOLE OF 2--CHLOROTHIOPHENE JOHN W. SCHICK INVENTOR.

I BY%MW% AGENT Patented Dec. 27, 1949 PRODUCTION OF THEENYLSODIUM COMPOUNDS John W. Schick, Camden, N. 1., assignorto Socony vacuum-z Oil; Company, Incorporated, a. corporation: of New'York Application November 14, 1946, SerialN'o. 709,868

17 Claims: 1iv This invention relates to a process' for pre paring thienylsodium compounds and, more par ticularly, is directed to a method for synthesizing thienylsodium.

It has heretofore been known that tliienylsodititles.

by the following-general.equation:

or. alkyl. radicals.

thienylsodium, for instamei; prepared from: chlosodium. synthesized according' to: previous proceduresinvolving. the use of organomercury com pounds. Whereas .theereactiond-ifiicultiesand: ex:- pense connected with" the preparation of: these: latter compounds: would prohibit. the; use. 01?

Thus; the

Ifhe: thienylsodium A particularly um can be prepared by the action of thiophene thi'enylsodium prepared in: this manner'onzacomwith organomercury compounds and sodium. mercial scale, the. process of: the present: inven- S'uclrmethods, .howevenhave been unsatisfactory, tion is a-pplicabl'eior thecommercial: manufacture resulting in. small. yields of thienylsodiumdespite of numerous: thiophenze products;

the.- relatively high. reaction temperatures emthienylsodium compounds of the present invenployed; andzthes excessively long; reaction periods tion are extremely useful: in. the: synthesis of'varof the order of: onedayor-more. These methods, ious derivatives ofi thiophenewhich', in turn,. find moreover, require the previous: preparation of eX- use in: the. manufacture. of' plastics, pharmaceupensive organomercury compounds and, hence do ticals, insecticides, dyes-, addition. agents for penot at all lend? themselves tothe production of. 5 troleurn fractions, odorants, synthetic lubricants; thienylsodium compounds; in' commercial; quanwaxes, extreme pressure: additives formineraloils,

. and; anti-foaming: agents;

It has: now been discovered that halogenated compounds produced in accordance: with the thiophene, compounds canbeyreacted with sodium method of this: invention. may be. further subunder particular conditions hereinafter described jest-ed t sultonation, carbonation,'halogenation; indetail to yield; a thienylsodium derivative.- In acylati'on; alkylation, hydrogenation, nitration, acco dan e w h t D 'O S Of t invention etc, to yield useful derivatives of'thiophene. The h m sDdiu-mi compounds are p p re y compounds-mayalso be'coupled or'condensed with acting a. halogen ted thiophene With; Sodium at, other molecules, be reacted with various other a temperature; between about C. and about 25 metals i general d r i ult t d f 15 Cri t pr n e of-an'inert r c e reactions which will be=recognizediby those. skilled Preferably, the: temperature at. which: the re.- in t action takes: place; willybe between about. C. In carrying out t reaction of: th i ti and abmlt Under Such ccnd'itions it: has sodium may: beintroducedintothe reaction mixbeerr found that a metathetiical reaction: takes so tu e a metallic sodium. or in the form of analloy place and theihalogerr atomioi the halothiophene containing sodiuminssubsbantia-l proportion refis replaced by. sodium; llhe thiophene. reactant rably as. its major component.

employed in; present PIOBESSI effective. means for introducin sodiuminto the 1521111 0116 more 31kmsubstimentsiit-bemg reaction: mixture is; from a. sodium amalgam. sentia'l however; fOIT'PuE-POSBST (If the? 6591117 Theuse-of a, sodium amalgam has generally been vention, that thereactant containv at least one i togive higher yields: ofthe desiredthienykhalogen snbstituen-t'. reaction; contemplated sodium colfnpnund use of sodi, -y' i-Ylventiml y acflflldingly'ibedesignated um. This increased yield of: product is dueprimarily tothe iactthat sodiumin; the form of an s s 4.0. amalgams is in.- an extremely finely sub-divided T 2N3 Na Nax state, presenting a very extensive. reaction sur- 1 face. In general, it may be stated that the re- R action, rate, and consequentlythe: yield, of de- Where X repr s nts a hal gen atom nd: the r sired. product, is, dependenton the particle: size maining substituents are either hydrogen" atoms of thesodium As arulathe. smaller theparticle size of sodium used, the faster was the rate. of

It s been found t y y g: outvthe reaction. Accordingly,.finely divided sodium, such above reaction in an inert: atmosphere and incth'e as sodium amalgam, sodium shot, or sodium sand, pr s e of n inert organic? l hs n is to be preferredfor-usein the present process. ether, toluene, benzene. etc, or: mixtures thereof, 5 It is essential that the temperatu t hi h hienylsodi m compo nds: n: be: r ily w the reaction ofsodium and halogenated thiophene pared in der ly higher" yields than h ve compounds is'carri'ed' out in accordance with this heretofore beenohtainedr Also, it is evident: that invention be between about 50 Cl and about 5 (3;. At: temperatures below- 50 C; no yield of the 0 rothiopl-iene, is moreieasiisraccsssiblethan; thienyiidesired -thineylsodiunr was obtained. Likewise; at

a temperature above 150 C. substantially no reaction yielding thienylsodium was found to take place. The decrease in yield at the higher temperatures is undoubtedly due to the fusion of the sodium particles employed, since the yield is substantially lowered above the melting point of sodium and decreases with higher temperatures up to a limit of about 150 0. Accordingly, for purposes of the present invention the temperature limits of C. and 150 C. are to be considered critical and the preferred temperature range is between about C. and about 90 C. The reaction may, if desired, be carried out under pressure, although ordinarily the process proceeds readily at atmospheric pressure. Usually when a pressure is employed, it will be sufiicient to maintain the reactants in the liquid phase, and this will be dependent on the particular temperature involved, said temperature necessarily being within the above stated limits.

Due to the high reactivity of sodium and the resultant thienylsodium compound, it is essential to exclude moisture and air from the reaction zone and to carry out the process of this invention in an inert atmosphere such as nitrogen or other of the inert gases. If the inert solvent employed is one of low boiling point, such as an ether, the vapor of said solvent may provide the inert atmosphere under which the reaction takes place.

After the reaction between the halogenated thiophene compound and sodium is finished, the thienylsodium compound which is formed thereby as a substance insoluble in benzene and the other inert organic solvents suitable for the process may be separated from the solution. However, for practical use of the thienylsodium compounds, it is unnecessary to separate the compounds from solution. It is advantageous to use the solution containing the thienylsodium compounds in suspended form immediately for performing further reactions. The thienylsodium compounds are of high reactivity and by bringing the thienylsodlum compounds in contact with substances containing reactive groups or atoms, a large number of different thiophene derivatives can be obtained, Suitable substances for carrying out these reactions are, for example, alkyl halides, nitriles, acid anhydrides, carbon dioxide, sulfur dioxide, compounds containing reactive hydrogen atoms which are able to be replaced by alkali metal, and the like. For example, by introducing carbon dioxide into a benzene solution containing thienylsodium, ields of thiophenic acid approaching 85 per cent can be obtained. As a general rule, it is desirable in the present reaction to employ chlorothiophene compounds, since these are more readily obtainable than the other halothiophene compounds and also chlorothiophene compounds generally give a higher yield of the desired thienylsodium compound than do the other halothiophenes.

The following detailed examples will serve to illustrate the method of preparing thienylsodium compounds in accordance with the present invention.

Example 1 A mixture of 29.5 grams (0.25 mole) of 2-chlorothiophene and 200 milliliters of dry toluene was slowly added over a period of 2 hours, at a reflux temperature of 112 C., to 13.75 grams (0.60 gram atom) of molten sodium in 100 milliliters of toluene. The reaction was carried out in an atmosphere of nitrogen. The reaction mixoil 4 ture began to darken immediately and after the addition was completed, the mixture was refluxed for an additional hour, after which it was cooled to 25 C. in an ice bath. The product resulting from said reaction was identified as 2-thienylsodium.

Such identification was effected by carbonating the product by the addition thereto of freshly crushed Dry Ice. The temperature was kept below 30 C. Thirty milliliters of methanol were then added to destroy the unreacted sodium and then 200 milliliters of distilled Water were cautiously added. The reaction mixture was then evaporated nearly to dryness and the residue acidified with 70 milliliters of concentrated hydrochloric acid. The resulting crystalline product was filtered and extracted with ethanol. The ethanol was then removed to yield a crystalline material weighing 10 grams (31 per cent yield) having a melting point of 125-126 C. and a neutral equivalent of 123.3. The calculated neutral equivalent for 2-thiophenecarboxylic acid was 128. The mixed melting point of this product with an authentic sample of 2-thiophenecarboXylic acid gave no depression.

Example 2 A mixture of 29.5 grams (0.25 mole) of 2 chlorothiophene and milliliters of anhydrous dibutyl ether was slowly added over a period of one hour to sodium amalgam sand containing 9 grams (0.39 gram atom) of sodium and 6 grams (0.03 gram atom) of mercury in 100 milliliters of anhydrous dibutyl ether which had been warmed at a temperature of 5055 C. After the addition was completed, the reaction mixture was stirred for an additional hour at the same temperature and then cooled to 25 C. The product resulting from said reaction was identified as 2- thienylsodium.

Such identification was effected by carbonat ing the product by the addition thereto of freshly crushed Dry Ice. Unreacted sodium was destroyed with 30 milliliters of ethanol, and then 150 milliliters of distilled water were cautiously added. The resulting aqueous layer was acidified with 70 milliliters of concentrated hydrochloric acid to yield a small amount of a crystalline product. The aqueous layer was then extracted with diethyl ether to remove the crystalline product therefrom. The ether was removed from said product by evaporation in a steam bath. The residue was dissolved in a minimum amount of hot water, decolorized with charcoal and quickly filtered. One gram of white needle-like crystals having a melting point of -l26 C. Was obtained. The mixed melting point of this material with an authentic sample of 2-thiophenecarboxylic acid gave no depression.

Example 3 A mixture of 119 grams (1.0 mole) of 2-chlorothiophene and 700 milliliters of benzene was slowly added over a period of 2 hours to sodium amalgam sand containing 35 grams (1.5 gram atoms) of sodium and 20 grams (0.1 gram atom) of mercury in 300 milliliters of benzene. The reaction mixture was warmed to 60-70? C. and after the addition was completed, the mixture was stirred for an additional 2 hours at the same temperature. The mixture was then cooled to 20 C. and the product resulting from said reaction was identified as 2-thienylsodium.

Such identification was effected by carbonating the product by the addition thereto of freshly crushedDryIce. As the carbonation proceeded; the temperature rose to 30 C. and then iellrapidly. Unreacted sodium .was destroyed with 100 milliliters of ethanol, and-400 milliliters of distilled water were then added cautiously. Acidification of the resulting aqueous layer with 170 milliliters of concentrated. hydrochloric acid yielded 75. grams. ('78 per cent yield) of Z-thiophenecarboxylic acid. A portion of this product was dissolved in a minimumamountof hot water, decal-- orized with charcoal and quickly filtered. Awhite crystalline product having a melting point of 125-126 C. was obtained. Thev mixed melting. point of this product with an authentic sample of 2-thiophenecarboxylic acid gave no depression.

Example. 4'

A mixture of 29.5 grams (0.25 mole) of 2-chlorothiophene and 200 milliliters of anisole was added slowly over a periodiof one hour to sodium amalgam sand containing 9 grams (0.39 gram atom) of sodium and figrams (0.03 gram atom) of mercury in'100 milliliters of. anisole. The re action mixture was warmedto a temperature of 50-55 0.. and a-iter'the addition wascompleted, thereaction mixture. was-stirred for an additional: hour at the sametemperature. The mixture was then cooled to C; .to lda product which was identified as 2-thienylsodium.

Such identification was effected by carbonating the product withzDryIce. Thev unreacted sodium was then destroyed by the addition of milIi-- liters of ethanol, andzlSO millilitersoidistilled water-were cautiously added. Acidification oi the resulting aqueous. layer with 70 milliliters of'concentrated hydrochloric acid yielded an oily layer. The resulting acidified solution was heated to near boiling and then quickly filtered. A crystalline product separated. from the cooled filtrate. The product was dissolved in a small amount of.

hot water, decolorized with charcoal, filtered and.-

cooled. White needle like crystals having a melting point 0112?" C. were obtained. The mixed melting point of this product with .an authentic.v sample of 2-thiophenecarboxylic acid gave sub.- stantially no depression, establishing the product as z-thiophenecarboxylic acid;

Example 5' A mixture of 118 grams-(1.0 mole) -of.2ch10r0 thiophe-ne and. 1000 milliliters of benzene was.

added. Acidificationof the-- resulting aqueouslayer with 125 milliliterszof concentrated hydro chloric acid yielded 10.8: grams (84 per cent yield) of aproductwhichxwas identified as2-thiophene carboxylic: acid.

Example 6 I A mixture of 118 grams (1.0 mole) .ci Z-chlorothiophene and 250 milliliters of benzene was added rapidly to freshly prepared sodium amal gam-sandcontaining 5012mm (lit gram atoms),

or sodium; andikflcrams (0.145. gram. atom) of? mercury. The reaction-mixture'was. warmed toa; reflux temperatureof 82 C. for; a period of 4:: hours. Theproduct" resulting from said reaction was identified as 2-thieny1sodium.

Such identification was effected by cooling the product told" C. and carbonated by the addition of pieces of freshly crushedDry Ice. The unreactedsodium was then destroyed by the addition of 100 milliliters of ethanol, after: which 350 milliliters of distilled water were cautiously added. Acidification of the resulting aqueous layer with 125 milliliters of concentrated hydrochloric acid yieldeda'lgrams ('70 per cent yield) ofa product which was identified as 2-thiophenecarboxylicacid;

Example 7 A mixture'oi'lm grams (1.0 mole) of Z-chlorothiophene and." 100. milliliters of benzene was added rapidly to freshly prepared sodium amalgamsand containing 50. grams- (2.1'l gram atoms) of sodium and 29 grams.(0.14:5 gram atom) of mercury. The-reaction mixturewas warmed to a reflux'temperature oi82" C. for a period of 4 hours. The product resulting fromsaid reaction was identified as; 2-thienylsodh1m.

Such identification was efiected by cooling the product to 10 C. and carbonated by the addition of small pieces of. freshly crushed Dry Ice. The unreacted sodium wasthen destroyed by the addition of 100 milliliters of ethanol, after which 350' milliliters of' distilled water were cautiously added. Acidification. of the resulting aqueous layer with. 125 milliliters of. concentrated hydrochloric acidyielded-25 grams (2.0 per cent yield) of .a product which was identified as Z-thiophenecarb oxylic acid.

An examination of theyields of. Z-thiophenecarboxylic acid obtained iniExamples 5, 6, and '7, where the-reaction wascarriedout under substantially identical conditionswith the exception of the amountz'of. solvent employed,.shows that the quantity ofsolvent present directly affectsthe yield of acid obtained, which, in turn, is indicative of the amount of desired thienylsodium compound obtained. This phenomenon will be readily apparent from the following table:

Ml. of Solvent Per cent Yield Example per Mole of 2- of 2-Thiophene Chlorothiophene carboxylic Acid "'phene present. The yield of acid upon further.

increaseein the-amount oi. solvent then remains substantially unchanged, other conditions re maining constant; While the further increasesinquantity ofsolvent used appear to have no detrimentalefiecton' the reaction; generally the amounts of solvent employed will not exceed about 10.00 milliliters permole of halogenated thiophene being treated. For most economical operation-:oftheprocess. ofthis invention under ther'nceferred't(imperz'tture conditionsoi" 60 C. to

90 C., the amount of solvent present will usually be greater than 200 milliliters per mole of halogenated thiophene and preferably between about 200 and about 700 milliliters per mole of halogenated thiophene.

I claim:

1. A process for preparing a thienylsodium compound comprising contacting sodium in the presence of an inert organic solvent with a com-' pound having the general formula:

s Raj IX R1 R1 where X is a halogen atom and substituents R1, R2, and R3 are selected from the group consisting of alkyl radicals and. hydrogen atoms, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 50 C. and about 150 C., thereby efiecting replacement of the halogen substituent of said compound with sodium.

- 2. A process for preparing a thienylsodium compound comprising contacting sodium in the presence of an inert organic solvent with a compound having the general formula:

PIP/SIX RQ'L R1 where X is achlorine atom and substituents R1, R2, and R3 are selected from the group consisting of alkyl radicals and hydrogen atoms, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 50 C. and about 150 C., thereby effecting replacement of the chlorine substituent of said compound with sodium.

i. A process for preparing a thienylsodium compound comprising contacting sodium in the presence of benzene with a compound having the general formula:

, s il F R L R,

where X is a halogen atom and substituents-R1, R2, and. R3 are selected from the group consisting of alkyl radicals and hydrogen atoms, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 50 C. and about 150 C., thereby effecting replacement of the halogen substituent of said compound with sodium.

- 5. A process for preparing a thienylsodium compound comprising contacting sodium in the presence of toluene with a compound having the general formula:

8 j T R L R,

where X is a halogen atom and substituents R1, R2, and R3 are selected from the group consisting of alkyl radicals and hydrogen atoms, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 50 C. and about 150 C., thereby effecting replacement of the halogen substituent of said compound with sodium.

6. A process for preparing a thienylsodium compound comprising contacting sodium with a compound having the general formula:

R Ix

where X is a halogen atom and substituents R1, R2, and R3 are selected from the group consisting of alkyl radicals and hydrogen atoms in the presence of at least 200 milliliters of an inert organic solvent per mole of said compound, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 50 C. and about 150 C., thereby effecting replacement of the halogen substituent of said compound with sodium.

7. A process for preparing a thienylsodium compound comprising contacting sodium with a compound having the general formula:

RIP-L- R1 where X is a halogen atom and substituents R1, R2, and R3 are selected from the group consisting of alkyl radicals and hydrogen atoms in the presence of between about 200 and about 700 milliliters of benzene per mole of said compound, maintaining the resulting reaction mixture under an inert atmosphere and at a temperature between about 60 C. and about C., thereby effecting replacement of the halogen substituent of said compound with sodium.

8. A process which comprises reacting sodium in the presence of an inert organic solvent with a monohalogenated thiophene at a temperature between about 50 C. and about C. thereby efiecting replacement of the halogen substituent of said thiophene reactant with sodium to yield a thienylsodium compound.

9. A process which comprises reacting sodium in the presence of an inert organic solvent with a monohalogenated thiophene at a temperature between about 60 C. and about 90 C. thereby effecting replacement of the halogen substituent of said thiophene reactant with sodium to yield a thienylsodium compound.

10. A process which comprises reacting sodium in the presence of an inert organic solvent with chlorothiophene at a temperature between about 50 C. and about 150 C. thereby effecting replacement of the chloro substituent of said thiophene reactant with sodium to yield a resulting compound of thienylsodium.

11. A process which comprises reacting sodium in the presence of an inert organic solvent with chlorothiophene at a temperature between about 60 C. and about 90 C. thereby effecting replacement of the chloro substituent of said thiophene reactant with sodium to yield a resulting compound of thienylsodium.

12. A process which comprises reacting sodium in the presence of benzene with a monohalogenated thiophene at a temperature between about 50 C. and about 90 0. thereby effecting replacement of the halogen substituent of said thiophene reactant with sodium to yield a thienylsodium compound.

13. A process which comprises reacting sodium in the presence of benzene with chlorothiophene at a temperature between about 60 C. and about 90 C. thereby effecting replacement of the chloro substituent of said thiophene reactant with sodium to yield a resulting compound of thienylsodium.

14. A process which comprises reacting sodium with a monohalogenated thiophene at a temperature between about 50 C. and about 150 C. in the presence of at least about 200 milliliters of an inert organic solvent per mole of said monohalogenated thiophene thereby effecting replacement of the halogen substituent of said thiophene reactant with sodium to yield a thienylsodium compound.

15. A process which comprises reacting sodium with chlorothiophene at a temperature between about 60 C. and about 90 C. in the presence of between about 200 and about 700 milliliters of benzene per mole of chlorothiophene thereby effecting replacement of the chloro substituent 10 of said thiophene reactant with sodium to yield a resulting compound of thienylsodium.

16. A process which comprises reacting a sodium amalgam in the presence of an inert organic solvent with a monohalogenated thiophene at a temperature between about 50 C. and about 150 C. thereby effecting replacement of the halogen substituent of said thiophene reactant with sodium to yield a thienylsodium compound.

17. A process which comprises reacting a sodium amalgam in the presence of an inert organic solvent with chlorothiophene at a temperature between about 50 C. and about 150 C. thereby effecting replacement of the chloro substituent of said thiophene reactant with sodium to yield a resulting compound of thienylsodium.

JOHN W. SCHICK.

REFERENCES CITED The following references are of record in the file of this \patent:

UNITED STATES PATENTS Name Date Morton June 27, 1939 OTHER REFERENCES Number 

